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Bone Grafting Technologies: Current and Prospective Therapies
No full textIt is estimated that more than 500,000 bone grafting surgeries occur yearly in the US to repair or replace defects caused by trauma, tumor resection, pathological degeneration and congenital malformations. Significant progress has been made in recent years to increase the technologies available for treating bone defects; however, because the field is vast and rapidly advancing, it is opportune to survey the technologies currently available and highlight promising future strategies. We performed a comprehensive literature review and subsequently divided the field into three areas: autografts, which are the gold standard in bone grafting, where bone tissue is harvested from another location in the body; allografts, which are bone grafts taken from cadavers or animals, that avoid the risks associated with autografts such as infection and donor site morbidity but have a high propensity for failure; and intelligently-engineered bone graft substitutes designed to improve graft incorporation. We also highlight advances in 3D printing, incorporation of stem cells, growth factors, and biomaterial scaffolds into bone grafting technologies. Our work is a timely summarization of the field and will assist clinicians and scientists in designing appropriate treatment strategies for patients requiring bone grafts
A Survey of Strategies to Modulate the Bone Morphogenetic Protein Signaling Pathway: Current and Future Perspectives.
Get PDFBone morphogenetic proteins (BMPs) constitute the largest subdivision of the TGF-β family of ligands and are unequivocally involved in regulating stem cell behavior. Appropriate regulation of canonical BMP signaling is critical for the development and homeostasis of numerous human organ systems, as aberrations in the BMP pathway or its regulation are increasingly associated with diverse human pathologies. In this review, we provide a wide-perspective on strategies that increase or decrease BMP signaling. We briefly outline the current FDA-approved approaches, highlight emerging next-generation technologies, and postulate prospective avenues for future investigation. We also detail how activating other pathways may indirectly modulate BMP signaling, with a particular emphasis on the relationship between the BMP and Activin/TGF-β pathways
Stringent Response Regulation of Virulence Factors in Vibrio Cholera
Get PDFVibrio cholerae colonization of the host requires stringent response activation of TCP, the Toxin-Coregulated Pilus
Cholera is an epidemic diarrheal disease caused by the Gramnegative bacterium Vibrio cholerae. In order to colonize a host, V. cholerae must express the toxin-coregulated pilus (TCP), and diarrheal symptoms are primarily produced by the virulence factor cholera toxin (CT). CT and TCP expression is regulated by the ToxR regulon. Components of the ToxR regulon include ToxT, a transcription factor that directly initiates transcription of the CT and TCP genes. Upstream regulators include the integral membrane proteins TcpP and ToxR, transcription factors necessary for expression of toxT. ToxR may also directly initiate transcription of the CT genes independently of ToxT. It is thought that TCP is required early in infection to colonize the small intestine and that CT is expressed later in order to produce diarrhea and escape the host. We found that stringent response, the universally-conserved low nutrient stress response, was necessary for colonization of the mouse small intestine. The hypothesis tested was that bacterial evaluation of nutrient environment regulated virulence genes through the stringent response control of the ToxR regulon. Deletions in the stringent response genes and of the ToxR regulon genes were made and these mutants used to determine where stringent response fit into the virulence gene regulatory system. Stringent response activated gene expression of virulence factors (those encoding CT and TCP) and some ToxR regulon components (toxT and tcpP) while it repressed others (toxR). The gene expression data was consistent with the requirement for stringent response-dependent colonization of the mouse; stringent response was required for TCP expression, with TCP required for colonization. The gene expression data showing that stringent response had differential effects on components in the ToxR regulon may explain how CT and TCP may be differentially regulated in infection despite being controlled by the same transcriptional activators
Sliding Arch Aortoplasty with Continuous Coronary Perfusion for Aortic Arch Hypoplasia Beyond Infancy
No full textClinical Relevance and Mechanisms of Antagonism Between the BMP and Activin/TGF-β Signaling Pathways.
Get PDFThe transforming growth factor β (TGF-β) superfamily is a large group of signaling molecules that participate in embryogenesis, organogenesis, and tissue homeostasis. These molecules are present in all animal genomes. Dysfunction in the regulation or activity of this superfamily\u27s components underlies numerous human diseases and developmental defects. There are 2 distinct arms downstream of the TGF-β superfamily ligands-the bone morphogenetic protein (BMP) and activin/TGF-β signaling pathways-and these 2 responses can oppose one another\u27s effects, most notably in disease states. However, studies have commonly focused on a single arm of the TGF-β superfamily, and the antagonism between these pathways is unknown in most physiologic and pathologic contexts. In this review, the authors summarize the clinically relevant scenarios in which the BMP and activin/TGF-β pathways reportedly oppose one another and identify several molecular mechanisms proposed to mediate this interaction. Particular attention is paid to experimental findings that may be informative to human pathology to highlight potential therapeutic approaches for future investigation
Puzzles in Bonding and Spectroscopy: the Case of Dicarbon
No full textThe unstable molecule C-2 has been of interest since its identification as the source of the Swan band features observable in the spectra of flames, carbon arcs, white dwarf stars, and comets, and it continues to serve as a focal point for experimental and theoretical discovery. Recent spectroscopic work has identified a quintet state of the molecule for the first time, while new insights into the bond order of C-2 in its ground state have been provided by sophisticated computational methods based on valence bond theory. This article gives a review of spectroscopic and computational work on C-2 including both historical background and the most recent discoveries
The Automated Discovery of Implied Causation Statements in Medical Research Literature: The Text-based Causation Signal caused by
No full textThe goal of the IMPLICATION project is to provide a tool that will keep the already busy Physicians or Scientists up to date on the latest discoveries, in their respective specialties by providing a faster way to access the latest material. The tool will automatically process text and extract from it critical information known as causation statements. These statements are identified with the help of causation signals, which are found in almost everything we read. A causation signal is a word or a phrase that links together the cause and the effect in a statement, and indicates the presence of causation in text. In this study, the causation signal caused by was identified in articles from PubMed. Using a pre-existing software tool, 300 abstracts were obtained from the PubMed database. The first fifty abstracts were used to identify the characteristics of causation statements and formulate the antecedent/consequent extraction rules, known as the pseudo-code extraction algorithm. To construct the algorithm, we used the process of iterative refinement: for each causation statement, the position of the signal caused by with respect to the antecedent and consequent was noted, which modified the pseudo-code, each time exceptions to the statement were observed. The common pattern observed in the initial set of statements was that the consequent occurred upstream of the signal while the antecedent occurred downstream of the signal. The pseudo-code extraction algorithm was tested on the rest of the abstracts to show its effectiveness. The algorithm correctly extracted the consequent 93.6% of the time and the antecedent 89.6% of the time. Using these results, the goal of identifying multiple chains of causation to provide Physicians and Scientists with accurate information quickly
Are Axon Reflex Responses Altered in Rosacea?
No full textSympathetic-like axon reflexes drive the initial increase in blood flow of the biphasic cutaneous vasodilation response of non-glabrous skin to local heating. It is currently unknown whether this process is involved in the etiology or altered in the pathology of facial flushing disorders, such as rosacea. The hypothesis that afferent responses (axon reflexes) to local triggers would be increased in rosacea-affected areas compared to both unaffected areas and control subjects was tested. In this pilot study, skin blood flow (laser-Doppler flowmetry) responses of one healthy subject and one otherwise healthy subject with rosacea to non-noxious local heating (Baseline for 5min, 32°C for 5min, and 42°C for 30 min) induction of axon reflex vasodilation in the forearm and cheek were measured and expressed as a percentage of maximum cutaneous vascular conductance (CVC = flux/mean arterial pressure). Additionally, sensation and thus the axon reflex was blocked in both forearm and cheek (topical lidocaine/prilocaine, 60- 90min) sites and skin blood flow responses were reassessed. Baseline and peak forearm skin blood flow differed between control (base = 12, peak = 89 %CVCmax) and rosacea (base = 2, peak = 80 %CVCmax) during heating without sensory blockade, but cheek skin blood flow values did not differ between subjects. During sensory blockade, peak forearm vasodilation was increased in rosacea (Control = 65, Rosacea = 77 %CVCmax), while cheek vasodilation was decreased (Control = 94, Rosacea = 84 %CVCmax). Additional subjects are needed to gain further insight to the role of sympathetic-like local axon reflexes in facial flushing disorders. Preliminarily, this pilot data suggests that there may be differences in axon reflex control of cutaneous vasodilation in rosacea-affected areas